Exploring BenzylethoxyAryl Urea Scaffolds for Multitarget Immunomodulation Therapies

Area of Science:

• Medicinal Chemistry
• Cancer Biology
• Immunology

Background:

• Cancer resistance to therapies is a significant challenge.
• Targeting multiple pathways, including angiogenesis and immune checkpoints, is crucial for effective cancer treatment.
• Developing novel small molecule immune potentiators (SMIPs) can enhance anti-tumor immunity.

Purpose of the Study:

• Synthesize and evaluate benzylethoxyaryl ureas as multitarget inhibitors of VEGFR-2 and PD-L1.
• Assess the antiproliferative activity and selective indexes of these compounds against various cell lines.
• Investigate the potential of these compounds as anti-cancer agents and immune potentiators.

Main Methods:

• Synthesis of thirteen benzylethoxyaryl ureas.
• Biological evaluation including antiproliferative assays on tumor, endothelial, immune, and non-tumor cell lines.
• Determination of selective indexes (SI) and assessment of CD11b expression and T-cell activity.

Main Results:

• Compounds with a p-substituted phenyl urea unit and diaryl carbamate showed high selective indexes.
• The designed ureas demonstrated good tumor antiangiogenic properties.
• Inhibition of CD11b expression and regulation of CD8 T-cell activity pathways were observed.

Conclusions:

• Benzylethoxyaryl ureas are effective multitarget inhibitors of VEGFR-2 and PD-L1.
• Selected compounds exhibit favorable anti-cancer and immune-potentiating properties.
• These ureas hold potential for the development of novel cancer immune treatments.